Maackiain Mimics Caloric Restriction through <i>aak-2</i>-Mediated Lipid Reduction in <i>Caenorhabditis elegans</i>
Obesity prevalence is becoming a serious global health and economic issue and is a major risk factor for concomitant diseases that worsen the quality and duration of life. Therefore, the urgency of the development of novel therapies is of a particular importance. A previous study of ours revealed th...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/24/17442 |
| _version_ | 1797380723824394240 |
|---|---|
| author | Saveta G. Mladenova Monika N. Todorova Martina S. Savova Milen I. Georgiev Liliya V. Mihaylova |
| author_facet | Saveta G. Mladenova Monika N. Todorova Martina S. Savova Milen I. Georgiev Liliya V. Mihaylova |
| author_sort | Saveta G. Mladenova |
| collection | DOAJ |
| description | Obesity prevalence is becoming a serious global health and economic issue and is a major risk factor for concomitant diseases that worsen the quality and duration of life. Therefore, the urgency of the development of novel therapies is of a particular importance. A previous study of ours revealed that the natural pterocarpan, maackiain (MACK), significantly inhibits adipogenic differentiation in human adipocytes through a peroxisome proliferator-activated receptor gamma (PPARγ)-dependent mechanism. Considering the observed anti-adipogenic potential of MACK, we aimed to further elucidate the molecular mechanisms that drive its biological activity in a <i>Caenorhabditis elegans</i> obesity model. Therefore, in the current study, the anti-obesogenic effect of MACK (25, 50, and 100 μM) was compared to orlistat (ORST, 12 μM) as a reference drug. Additionally, the hybrid combination between the ORST (12 μM) and MACK (100 μM) was assessed for suspected synergistic interaction. Mechanistically, the observed anti-obesogenic effect of MACK was mediated through the upregulation of the key metabolic regulators, namely, the nuclear hormone receptor 49 (<i>nhr-49</i>) that is a functional homologue of the mammalian PPARs and the AMP-activated protein kinase (aak-2/AMPK) in <i>C. elegans</i>. Collectively, our investigation indicates that MACK has the potential to limit lipid accumulation and control obesity that deserves future developments. |
| first_indexed | 2024-03-08T20:42:09Z |
| format | Article |
| id | doaj.art-cce468c4cfe04525b577ea5d1c096f99 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T20:42:09Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cce468c4cfe04525b577ea5d1c096f992023-12-22T14:14:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241744210.3390/ijms242417442Maackiain Mimics Caloric Restriction through <i>aak-2</i>-Mediated Lipid Reduction in <i>Caenorhabditis elegans</i>Saveta G. Mladenova0Monika N. Todorova1Martina S. Savova2Milen I. Georgiev3Liliya V. Mihaylova4Independent Researcher, 1000 Sofia, BulgariaLaboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, BulgariaLaboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, BulgariaLaboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, BulgariaLaboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, BulgariaObesity prevalence is becoming a serious global health and economic issue and is a major risk factor for concomitant diseases that worsen the quality and duration of life. Therefore, the urgency of the development of novel therapies is of a particular importance. A previous study of ours revealed that the natural pterocarpan, maackiain (MACK), significantly inhibits adipogenic differentiation in human adipocytes through a peroxisome proliferator-activated receptor gamma (PPARγ)-dependent mechanism. Considering the observed anti-adipogenic potential of MACK, we aimed to further elucidate the molecular mechanisms that drive its biological activity in a <i>Caenorhabditis elegans</i> obesity model. Therefore, in the current study, the anti-obesogenic effect of MACK (25, 50, and 100 μM) was compared to orlistat (ORST, 12 μM) as a reference drug. Additionally, the hybrid combination between the ORST (12 μM) and MACK (100 μM) was assessed for suspected synergistic interaction. Mechanistically, the observed anti-obesogenic effect of MACK was mediated through the upregulation of the key metabolic regulators, namely, the nuclear hormone receptor 49 (<i>nhr-49</i>) that is a functional homologue of the mammalian PPARs and the AMP-activated protein kinase (aak-2/AMPK) in <i>C. elegans</i>. Collectively, our investigation indicates that MACK has the potential to limit lipid accumulation and control obesity that deserves future developments.https://www.mdpi.com/1422-0067/24/24/17442obesitylipid accumulation<i>Caenorhabditis elegans</i>orlistatmaackiainAMPK |
| spellingShingle | Saveta G. Mladenova Monika N. Todorova Martina S. Savova Milen I. Georgiev Liliya V. Mihaylova Maackiain Mimics Caloric Restriction through <i>aak-2</i>-Mediated Lipid Reduction in <i>Caenorhabditis elegans</i> International Journal of Molecular Sciences obesity lipid accumulation <i>Caenorhabditis elegans</i> orlistat maackiain AMPK |
| title | Maackiain Mimics Caloric Restriction through <i>aak-2</i>-Mediated Lipid Reduction in <i>Caenorhabditis elegans</i> |
| title_full | Maackiain Mimics Caloric Restriction through <i>aak-2</i>-Mediated Lipid Reduction in <i>Caenorhabditis elegans</i> |
| title_fullStr | Maackiain Mimics Caloric Restriction through <i>aak-2</i>-Mediated Lipid Reduction in <i>Caenorhabditis elegans</i> |
| title_full_unstemmed | Maackiain Mimics Caloric Restriction through <i>aak-2</i>-Mediated Lipid Reduction in <i>Caenorhabditis elegans</i> |
| title_short | Maackiain Mimics Caloric Restriction through <i>aak-2</i>-Mediated Lipid Reduction in <i>Caenorhabditis elegans</i> |
| title_sort | maackiain mimics caloric restriction through i aak 2 i mediated lipid reduction in i caenorhabditis elegans i |
| topic | obesity lipid accumulation <i>Caenorhabditis elegans</i> orlistat maackiain AMPK |
| url | https://www.mdpi.com/1422-0067/24/24/17442 |
| work_keys_str_mv | AT savetagmladenova maackiainmimicscaloricrestrictionthroughiaak2imediatedlipidreductioninicaenorhabditiselegansi AT monikantodorova maackiainmimicscaloricrestrictionthroughiaak2imediatedlipidreductioninicaenorhabditiselegansi AT martinassavova maackiainmimicscaloricrestrictionthroughiaak2imediatedlipidreductioninicaenorhabditiselegansi AT milenigeorgiev maackiainmimicscaloricrestrictionthroughiaak2imediatedlipidreductioninicaenorhabditiselegansi AT liliyavmihaylova maackiainmimicscaloricrestrictionthroughiaak2imediatedlipidreductioninicaenorhabditiselegansi |